This invention relates to the synthesis of secondary and tertiary amines containing phosphonyl and carbonyl groups and, more particularly, to an improved process for producing N-phosphonomethylglycine or derivatives thereof by reductive alkylation.
N-Phosphonomethylglycine, known in the agricultural chemical art as glyphosate, is a highly effective and commercially important phytotoxicant useful in controlling the growth of germinating seeds, emerging seedlings, maturing and established woody and herbaceous vegetation, and aquatic plants. Glyphosate and salts thereof are conveniently applied in the form of an aqueous solution as a post-emergent phytotoxicant or herbicide for the control of growth of one or more monocotyledonous species and one or more dicotyledonous species. Moreover, such compounds are characterized by broad spectrum activity, i.e., they control the growth of a wide variety of plants, including but not limited to ferns, conifers, aquatic monocotyledons, and dicotyledons.
Hershman, U.S. Pat. No. 3,969,398, describes a process for preparing glyphosate in which iminodiacetic acid is reacted with formaldehyde and phosphorous acid to produce N-phosphonomethyliminodiacetic acid as an intermediate. This is then oxidized to produce glyphosate.
Gaertner, Canadian Pat. No. 1,039,739, describes a process for producing glyphosate by reacting aminomethylphosphonic acid and esters with glyoxal or glyoxylic acid to form a carbonylaldiminomethanephosphonate. Thereafter, the carbonylaldiminomethanephosphonate is subjected to catalytic hydrogenation to reduce the double bond and produce glyphosate or esters. The ester groups are then hydrolyzed to produce N-phosphonomethylglycine. Both the condensation of aminomethylphosphonate with aldehyde and catalytic hydrogenation of the resultant imine are carried out in organic solvents. For the condensation reaction, the solvent is an aromatic hydrocarbon, such as benzene, toluene, or xylene, while catalytic hydrogenation is typically carried out in an alcohol.
Franz, U.S. Pat. No. 3,799,758, describes the preparation of glyphosate by reaction of ethyl glycinate, formaldehyde, and diethyl phosphite. Alternative processes described by Franz include phosphonomethylation of glycine with chloromethylphosphonic acid in the presence of sodium hydroxide and oxidation of N-phosphinomethylglycine with mercuric chloride.
Gaertner, U.S. Pat. No. 3,927,080, describes the production of glyphosate by acid hydrolysis of N-t-butyl-N-phosphonomethylglycine or its esters. Tertiary butyl amine is reacted with a bromoacetate ester to produce an ester of N-t-butylglycine which is in turn reacted with formaldehyde and phosphorous acid to produce the N-t-butyl-N-phosphonomethylglycine precursor.
Ehrat, U.S. Pat. No. 4,237,065, describes a process in which glycine is condensed with formaldehyde in the presence of a tertiary base to produce N-methyl glycine or N-methylene glycine, and the latter is in turn reacted with phosphorous acid to produce glyphosate.
Pfliegle et al, U.S. Pat. No. 4,065,491, discloses a process in which N-phosphonomethylglycine is prepared by condensation of glycine, formaldehyde, and a dialkyl phosphite in an aqueous alkaline medium to form an N-phosphonomethylglycine dialkyl ester. The latter is hydrolyzed with a mineral acid to produce glyphosate.
While Gaertner, as described in his aforesaid Canadian patent, achieved monoalkylation of aminomethylphosphonic acid by the sequential process of first condensing aminomethylphosphonic acid or its esters with glyoxylic acid or its esters to produce the aldimine and thereafter subjecting the aldimine to catalytic hydrogenation, there are other references which describe the in situ reduction of the condensation products of various amines and aldehydes. Such condensation and in situ reduction is generally referred to in the art as reductive alkylation. However, when the aldimino structure obtained by condensation of a primary amine with an aldehyde is reduced in situ, the resultant secondary amine can further react with the aldehyde to produce an aminal which is in turn reduced by hydrogenolysis resulting in formation of a tertiary amine. Thus, the result is typically substantial dialkylation rather than the substantially exclusive monoalkylation that is preferred in the preparation of an end product, such as glyphosate.
Ikutani, "Studies of the N-Oxides of N,N-Dialkyl Amino Acids. II. The Syntheses of N,N-Dialkylglycine and Corresponding N-Oxides", Bulletin of the Chemical Society of Japan, 42, pp. 2230-2332, (1969) reports the reductive condensation of glycine with various aliphatic aldehydes. Only with relatively hindered aldehydes did Ikutani recover any monoalkylated product after reactions at 40.degree. C. to 50.degree. C. for periods of 3 to 9 hours. In the case of acetaldehyde, propionaldehyde, and n-butyraldehyde, at best a trace of monoalkyl product was recovered while the dialkyl yields ranged from 41% to 83%.
Bowman, "N-Substituted Amino Acids. Part II. The Reductive Alkylation of Amino Acids", Journal of the Chemical Society, Part 2, p. 1346, (1950) reported that experiments on the alkylation of glycine by means of acetaldehyde, propionaldehyde, n-butanal, and n-heptanal, under conditions favorable to the formation of monoalkyl derivatives, failed to reveal any evidence of partial alkylation.
Moser, U.S. Pat. No. 4,369,142, describes a process for the preparation of N-phosphonomethylglycine in which aminomethylphosphonic acid is reacted in aqueous medium with glyoxal in the presence of sulfur dioxide.
In DE No. 2,725,669 there is disclosed a process for the preparation of secondary amines under hydrogenation conditions in the presence of a catalyst comprising nickel or cobalt and a quaternary ammonium compound. High yields are reported.
Mono-substituted amino acids, such as glycines and alanines, are prepared by a process disclosed in EPO No. 0079767 wherein a primary amino group and a ketone are reacted under reductive condensation conditions in the presence of a reductant and a hydrogenation catalyst under conditions of elevated temperature and superatmospheric conditions. Nobel metal catalysts are described and the preferred catalyst is palladium on carbon.